SLIPPERS Reconsidered: Clinical, Radiological, and Pathological Overlap with PACNS-A Case Report.

Background and Clinical Significance: SLIPPERS syndrome (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids) was first described in 2015 as a variant of CLIPPERS restricted to supratentorial regions. Only a few cases have been reported so far, and its distinction from primary angiitis of the central nervous system (PACNS) remains challenging, as both may present with overlapping clinical, radiological, and histopathological features. We report two patients initially diagnosed with SLIPPERS but finally fulfilling the diagnostic criteria for PACNS, highlighting the complexity of the differential diagnosis. Case Presentation: The first patient was a 49-year-old woman who presented with seizures, memory impairment, and facial neuralgia. MRI showed multiple cortico-subcortical and deep nodular lesions in the left hemisphere with gadolinium enhancement. Brain biopsy revealed a T-cell-predominant lymphocytic vascular infiltrate. She responded to corticosteroids but later relapsed, requiring methotrexate for long-term immunosuppression, with no further recurrences during seven years of follow-up. The second patient was a 64-year-old man with hypertension, dyslipidemia, and alcohol use who developed repeated focal-to-generalized seizures. MRI disclosed multifocal nodular gadolinium-enhancing right hemispheric lesions, with SWI microhemorrhages. Biopsy demonstrated transmural T-cell vasculitic infiltrates. He responded to corticosteroids and methotrexate, but radiological progression at 14 months prompted replacement with cyclophosphamide. Conclusions: There is a considerable clinical, radiological, and histological overlap between SLIPPERS and PACNS. Careful analysis of advanced MRI sequences, particularly angiographic and vessel-wall imaging studies, combined with meticulous histopathological analysis, is essential to avoid misdiagnosis. These similarities suggest that some cases attributed to SLIPPERS may, in fact, correspond to variants of PACNS.